Abstract 4113: Classification of patient-specific sensitivity to immunotherapies by <i>ex vivo</i> tumor testing
Authors: Lieke Johanna Ceton, Marta Garcia Montero, Fanny Grillet, Dieudonné J. van der Meer, Willemijn Vader, Anne van Altena, Cor D. de Kroon, Nelleke Ottevanger, Judith Kroep
Journal: Cancer Research (2023)

Abstract Background: Immunotherapy has brought great progress with durable responses for cancers that were difficult to treat. However, it remains challenging to select sensitive patients upfront. PD-L1 expression, TMB and MSI/MSS status, do not optimally differentiate between the potential sensitivity to the individual immunotherapies. Purpose: We aim to improve stratification of patients for immunotherapy through classification of patient-specific tumor sensitivity based on 3D ex vivo drug measurement. Material: Our study includes 108 Patients with predominantly ovarian carcinoma (81/108). Tumor tissue was collected in ongoing clinical trials from biopsies, ascites or pleural fluid. Five immune checkpoint inhibitors and a STING pathway activator were tested. Method: Fresh tumor clusters were seeded into 384 well plates and exposed to different immunotherapies, while preserving the TME. Tumor killing and immune cell proliferation were measured using 3D image analysis. Ex vivo tumor sensitivity was classified as no response (&amp;lt;10%), weak (10-20%), strong (20-50%), and very strong (&amp;gt;50%), based on percentage tumor killing and statistical significance (p-value: * &amp;lt; 0.05, ** &amp;lt; 3.33e-4). Results: Differential patient response profiles were observed (Table 1). For the current cohort, we measured a highly significant immunotherapy response for ~30% of the samples. The assay has a technical success rate of 89%. Conclusion: This study reports the development of a robust ex vivo tumor testing platform that classified patient-specific sensitivity to 6 immunotherapies for over 100 patients, demonstrating the potential of ex vivo tumor testing to optimize patient stratification for immunotherapy. Discussion: The platform enables improved efficiency in clinical development of novel treatments and supports treatment decisions in the clinic. Clinical trials are ongoing to establish the correlation of our testing with patients' response to immunotherapy in lung cancer. Overview of ex vivo immunotherapy response per category 1Therapy # Samples tested % Response No response Weak Strong Very strong SEA (control) 108 43% (30%**) 62 5 19 22 CD3/CD28 Dynabeads (control) 18 33% (17%**) 12 1 5 0 Pembrolizumab 89 16% (8%**) 75 6 5 3 Nivolumab 72 10% (4%**) 65 1 5 1 Ipilimumab 97 20% (11%**) 78 4 10 5 Atezolizumab 62 15% (11%**) 53 1 4 4 Durvalumab 52 2% (0%**) 51 1 0 0 ADU-S100 60 37% (27%**) 38 5 9 8 Citation Format: Lieke Johanna Ceton, Marta Garcia Montero, Fanny Grillet, Dieudonné J. van der Meer, Willemijn Vader, Anne van Altena, Cor D. de Kroon, Nelleke Ottevanger, Judith Kroep. Classification of patient-specific sensitivity to immunotherapies by ex vivo tumor testing. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4113.